WH2 and proline-rich domains of WASP-family proteins collaborate to accelerate actin filament elongation.

WASP-family proteins are known to promote assembly of branched actin networks by stimulating the filament-nucleating activity of the Arp2/3 complex. Here, we show that WASP-family proteins also function as polymerases that accelerate elongation of uncapped actin filaments. When clustered on a surface, WASP-family proteins can drive branched actin networks to grow much faster than they could by direct incorporation of soluble monomers. This polymerase activity arises from the coordinated action of two regulatory sequences: (i) a WASP homology 2 (WH2) domain that binds actin, and (ii) a proline-rich sequence that binds profilin-actin complexes. In the absence of profilin, WH2 domains are sufficient to accelerate filament elongation, but in the presence of profilin, proline-rich sequences are required to support polymerase activity by (i) bringing polymerization-competent actin monomers in proximity to growing filament ends, and (ii) promoting shuttling of actin monomers from profilin-actin complexes onto nearby WH2 domains. Unoccupied WH2 domains transiently associate with free filament ends, preventing their growth and dynamically tethering the branched actin network to the WASP-family proteins that create it. Collaboration between WH2 and proline-rich sequences thus strikes a balance between filament growth and tethering. Our work expands the number of critical roles that WASP-family proteins play in the assembly of branched actin networks to at least three: (i) promoting dendritic nucleation; (ii) linking actin networks to membranes; and (iii) accelerating filament elongation

Integrated landscape initiatives in Europe: Multi-sector collaboration in multi-functional landscapes

Landscapes are linked to human well-being in a multitude of ways, some of which are challenged by global market forces and traditional management approaches. In response to this situation there has been a rise in local initiatives to sustain the values of landscape. The aim of this paper is to provide a systematic analysis of the spectrum of these initiatives in Europe in terms of patterns of organisation, participants, resources, problems, and landscape values addressed. This review collects examples of integrated landscape initiatives from all over Europe through systematic internet key word searches and canvassing of European umbrella organisations; followed by an online survey of representatives from the identified initiatives (n = 71). Our results show that the most relevant characteristics of integrated landscape initiatives in Europe are: a holistic approach to landscape management (acting in multifunctional landscapes and combining different objectives), the involvement and coordination of different sectors and stakeholders at many levels, and the role as agents of awareness raising and learning hubs. Integrated landscape initiatives mainly depend on impulses of local civil society. Identified barriers to their work include a lack of funding and institutional support. Therefore, political and societal action is needed to increase their effectiveness

CLIP-170 tracks growing microtubule ends by dynamically recognizing composite EB1/tubulin-binding sites

The microtubule cytoskeleton is crucial for the internal organization of eukaryotic cells. Several microtubule-associated proteins link microtubules to subcellular structures. A subclass of these proteins, the plus end–binding proteins (+TIPs), selectively binds to the growing plus ends of microtubules. Here, we reconstitute a vertebrate plus end tracking system composed of the most prominent +TIPs, end-binding protein 1 (EB1) and CLIP-170, in vitro and dissect their end-tracking mechanism. We find that EB1 autonomously recognizes specific binding sites present at growing microtubule ends. In contrast, CLIP-170 does not end-track by itself but requires EB1. CLIP-170 recognizes and turns over rapidly on composite binding sites constituted by end-accumulated EB1 and tyrosinated α-tubulin. In contrast to its fission yeast orthologue Tip1, dynamic end tracking of CLIP-170 does not require the activity of a molecular motor. Our results demonstrate evolutionary diversity of the plus end recognition mechanism of CLIP-170 family members, whereas the autonomous end-tracking mechanism of EB family members is conserved

Changes in self-schema structure in cognitive therapy for major depressive disorder: a randomized clinical trial.

Negative cognitive structure (particularly for interpersonal content) has been shown in some research to persist past a current episode of depression and potentially to be a stable marker of vulnerability for depression (D. J. A. Dozois, 2007; D. J. A. Dozois & K. S. Dobson, 2001a). Given that cognitive therapy (CT) is highly effective for treating the acute phase of a depressive episode and that this treatment also reduces the risk of relapse and recurrence, it is possible that CT may alter these stable cognitive structures. In the current study, patients were randomly assigned to CT+ pharmacotherapy (n = 21) or to pharmacotherapy alone (n = 21). Both groups evidenced significant and similar reductions in level of depression (as measured with the Beck Depression Inventory-II and the Hamilton Rating Scale for Depression), as well as automatic thoughts and dysfunctional attitudes. However, group differences were found on cognitive organization in favor of individuals who received the combination of CT+ pharmacotherapy. The implications of these results for understanding mechanisms of change in therapy and the prophylactic nature of CT are discussed

Microtubule depolymerization by the kinesin-8 motor Kip3p: a mathematical model

Proteins from the kinesin-8 family promote microtubule (MT) depolymerization, a process thought to be important for the control of microtubule length in living cells. In addition to this MT shortening activity, kinesin 8s are motors that show plus-end directed motility on MTs. Here we describe a simple model that incorporates directional motion and destabilization of the MT plus end by kinesin 8. Our model quantitatively reproduces the key features of length-vs-time traces for stabilized MTs in the presence of purified kinesin 8, including length-dependent depolymerization. Comparison of model predictions with experiments suggests that kinesin 8 depolymerizes processively, i.e., one motor can remove multiple tubulin dimers from a stabilized MT. Fluctuations in MT length as a function of time are related to depolymerization processivity. We have also determined the parameter regime in which the rate of MT depolymerization is length dependent: length-dependent depolymerization occurs only when MTs are sufficiently short; this crossover is sensitive to the bulk motor concentration.Comment: 34 pages, 11 figure

Changes in Core Beliefs (Early Maladaptive Schemas) and Self-Representation in Cognitive Therapy and Pharmacotherapy for Depression

Randomized clinical trials suggest that cognitive therapy (CT) is comparable to antidepressant medication for the acute treatment of depression. Compelling data also indicate that CT has an added prophylactic benefit relative to pharmacotherapy (PT). The purpose of this study was to examine cognitive change in CT for depression. Participants (N = 42) met diagnostic criteria for a current major depressive episode and were randomly assigned to CT + PT or PT. Participants completed indices of depressive symptomatology, core beliefs (i.e., early maladaptive schemas), and self-attribute redundancy before and after therapy. Self-attribute redundancy was conceptualized as a form of schema organization and operationalized as the number of similar traits that permeate different aspects of self (e.g., as a partner, friend, employee). Treatment change was evident in both groups on self-reported core belief domains, with few between-group differences. Although no group differences were found on attribute redundancy at pre-treatment, there was a significant increase in positive redundancy at post-treatment favoring CT + PT. No group differences were found for negative content. These findings suggest that something about CT may uniquely impact self-representation and that CT may operate by bolstering compensatory schemas

Self-oriented perfectionism and socially prescribed perfectionism: Differential relationships with intrinsic and extrinsic motivation and test anxiety

Previous studies suggest that self-oriented and socially prescribed perfectionism show differential relationships with intrinsic–extrinsic motivation and test anxiety, but the findings are ambiguous. Moreover, they ignored that test anxiety is multidimensional. Consequently, the present study re-investigated the relationships in 104 university students examining how the two forms of perfectionism are related to intrinsic–extrinsic motivation and multidimensional test anxiety (worry, emotionality, interference, lack of confidence, and total anxiety). Regarding motivation, self-oriented perfectionism showed positive correlations with intrinsic reasons for studying, and socially prescribed perfectionism positive correlations with extrinsic reasons. Regarding test anxiety, only socially prescribed perfectionism showed positive correlations with total anxiety. Moreover, socially prescribed perfectionism showed positive correlations with interference and lack of confidence, whereas self-oriented perfectionism showed positive correlations with worry, but negative correlations with interference and lack of confidence. The findings confirm that socially prescribed perfectionism is a maladaptive form of perfectionism associated with extrinsic motivation for studying and higher anxiety in exams. Self-oriented perfectionism, however, is an ambivalent form associated with intrinsic motivation for studying and with both higher and lower anxiety (higher worry, lower interference, lower lack of confidence) in exams

Scattering of Noncommutative Waves and Solitons in a Supersymmetric Chiral Model in 2+1 Dimensions

Interactions of noncommutative waves and solitons in 2+1 dimensions can be analyzed exactly for a supersymmetric and integrable U(n) chiral model extending the Ward model. Using the Moyal-deformed dressing method in an antichiral superspace, we construct explicit time-dependent solutions of its noncommutative field equations by iteratively solving linear equations. The approach is illustrated by presenting scattering configurations for two noncommutative U(2) plane waves and for two noncommutative U(2) solitons as well as by producing a noncommutative U(1) two-soliton bound state.Comment: 1+13 pages; v2: reference added, version published in JHE

The effects of financialisation and financial development on investment: Evidence from firm-level data in Europe

In this paper we estimate the effects of financialization on physical investment in selected western European countries using panel data based on the balance-sheets of publicly listed non-financial companies (NFCs) supplied by Worldscope for the period 1995-2015. We find robust evidence of an adverse effect of both financial payments (interests and dividends) and financial incomes on investment in fixed assets by the NFCs. This finding is robust for both the pool of all Western European firms and single country estimations. The negative impacts of financial incomes are non-linear with respect to the companies’ size: financial incomes crowd-out investment in large companies, and have a positive effect on the investment of only small, relatively more credit-constrained companies. Moreover, we find that a higher degree of financial development is associated with a stronger negative effect of financial incomes on companies’ investment. This finding challenges the common wisdom on ‘finance-growth nexus’. Our findings support the ‘financialization thesis’ that the increasing orientation of the non-financial sector towards financial activities is ultimately leading to lower physical investment, hence to stagnant or fragile growth, as well as long term stagnation in productivity

Dispersionless limit of the noncommutative potential KP hierarchy and solutions of the pseudodual chiral model in 2+1 dimensions

The usual dispersionless limit of the KP hierarchy does not work in the case where the dependent variable has values in a noncommutative (e.g. matrix) algebra. Passing over to the potential KP hierarchy, there is a corresponding scaling limit in the noncommutative case, which turns out to be the hierarchy of a `pseudodual chiral model' in 2+1 dimensions (`pseudodual' to a hierarchy extending Ward's (modified) integrable chiral model). Applying the scaling procedure to a method generating exact solutions of a matrix (potential) KP hierarchy from solutions of a matrix linear heat hierarchy, leads to a corresponding method that generates exact solutions of the matrix dispersionless potential KP hierarchy, i.e. the pseudodual chiral model hierarchy. We use this result to construct classes of exact solutions of the su(m) pseudodual chiral model in 2+1 dimensions, including various multiple lump configurations.Comment: 37 pages, 10 figures, 2nd version: some extensions (Fig 3, Appendix A, additional references), 3rd version: some minor changes, additional reference